Relaxin is an ovarian peptide hormone that is responsible for those tissue modifications that result in birth canal widening just prior to parturition. Relaxin is produced in the corpus luteum of pregnancy or in the placenta and is a disulfide homolog of insulin that exhibits neither biological insulin activity nor crossreactivity to antibodies raised against insulin. Besides the involvement in parturition relaxin may play a role in fertility in that the implantation of an ovum into the endometrium appears to be a relaxin-mediated process and sperm motility appears to be enhanced in the presence of relaxin. It has also been reported that relaxin exhibits an insulin-sparing activity during pregnancy and thus may be a potential drug for the treatment of pregnancy diabetes. The studies proposed here are aimed at an understanding of the relationship of relaxin structure to its various functions. The plan is to chemically dissect and reconstitute various aspects of the relaxin surface and to measure the effect of such modifications on the structural integrity and the biological activity of the molecule. One of the immediate goals is to identify the receptor interaction site of relaxin and to modify this interaction site in such a way that a covalent link with the receptor may be established. Chemical recognition sites have been added to the relaxin molecule in places where they do not interfere with biological activity and these sites should now serve to isolate the covalently-linked relaxin receptor complex. Attempts will then be made to obtain partial sequence information concerning the relaxin receptor that would eventually aid in the construction of a nucleotide probe with which a relaxin receptor-coding sequence may be isolated from the appropriate gene library.
| Yang, S; Heyn, H; Zhang, Y Z et al. (1993) The expression of human relaxin in yeast. Arch Biochem Biophys 300:734-7 |
| Bullesbach, E E; Yang, S; Schwabe, C (1992) The receptor-binding site of human relaxin II. A dual prong-binding mechanism. J Biol Chem 267:22957-60 |
| Yang, S; Rembiesa, B; Bullesbach, E E et al. (1992) Relaxin receptors in mice: demonstration of ligand binding in symphyseal tissues and uterine membrane fragments. Endocrinology 130:179-85 |
| Bullesbach, E E; Schwabe, C (1991) Total synthesis of human relaxin and human relaxin derivatives by solid-phase peptide synthesis and site-directed chain combination. J Biol Chem 266:10754-61 |
| Schwabe, C; Bullesbach, E E (1990) Relaxin. Comp Biochem Physiol B 96:15-21 |
| Bullesbach, E E; Schwabe, C (1990) Monobiotinylated relaxins. Preparation and chemical properties of the mono(biotinyl-epsilon-aminohexanoyl) porcine relaxin. Int J Pept Protein Res 35:416-23 |
